Prodrug means a pharmaceutical product that is converted to an active ingredient as a result of a reaction with an enzyme, gastric acid, etc., in a living body. Preparation of such a prodrug from a pharmaceutical product is carried out for the purposes of: (1) improving absorbability into a body, (2) reducing side effects, (3) allowing it to act in a specific organ, (4) sustaining the action, and the like.
1-(Acyloxy)alkoxycarbonyl group has been used for conversion of various pharmaceutical molecules having an amino group or the like to prodrugs. A pharmaceutical molecule having an amino group is converted to a prodrug by introducing such a 1-(acyloxy)alkoxycarbonyl group, so that the pharmaceutical molecule is converted to a 1-(acyloxy)alkyl carbamate derivative (Non Patent Literatures 1 and 2).
Patent Literature 1 discloses 1-(acyloxy)alkyl carbamate derivatives (Examples 20, 22, 23, 27, 28, 29, 30, 31, and 32 of Patent Literature 1) as prodrugs of compounds showing TAFIa inhibitory activity (Examples 15 and 40 of Patent Literature 1).
As methods of synthesizing 1-(acyloxy)alkyl carbamate derivatives, the methods disclosed in Patent Literatures 2 to 8, etc. are known. However, these methods have been disadvantageous in that they need multi-stage reaction steps, in that they provide a low yield, in that they generate by-products, which are hardly removed, etc.